Apollon gene silencing induces apoptosis in breast cancer cells via p53 stabilisation and caspase-3 activation

Paola Poma, Gandellini, Orlotti, Alessia Lopergolo, Marzia Pennati, Marco Folini, Nadia Zaffaroni, Maria Grazia Daidone

Risultato della ricerca: Articlepeer review

42 Citazioni (Scopus)

Abstract

We analysed the effects of small interfering RNA (siRNA)-mediated silencing of Apollon, a member of the inhibitors of apoptosisprotein family, on the proliferative potential and ability of human breast cancer cell lines to undergo apoptosis. In wild-type p53ZR75.1 cells, Apollon knockdown resulted in a marked, time-dependent decline of cell growth and an increased rate of apoptosis,which was associated with p53 stabilisation and activation of the mitochondrial-dependent apoptotic pathway. Pre-incubation of cellswith a p53-specific siRNA resulted in a partial rescue of cell growth inhibition, as well as in a marked reduction of the apoptoticresponse, indicating p53 as a major player in cell growth impairment consequent on Apollon silencing. Apollon knockdown inducedconsistently less pronounced anti-proliferative and pro-apoptotic effects in mutant p53 MDA-MB-231 cells than in ZR75.1 cells.Furthermore, the activation of caspase-3 seemed to be essential for the induction of apoptosis after Apollon knockdown, as theApollon-specific siRNA had no effect on the viability of caspase-3-deficient, wild-type p53 MCF-7 cells or the ZR75.1 cells after RNAinterference-mediated caspase-3 silencing. Our results indicate that p53 stabilisation and caspase-3 activation concur to determinethe apoptotic response mediated by Apollon knockdown in breast cancer cells, and suggest Apollon to be a potential newtherapeutic target for this malignancy.
Lingua originaleEnglish
pagine (da-a)739-746
Numero di pagine8
RivistaBritish Journal of Cancer
Volume100
Stato di pubblicazionePublished - 2009

All Science Journal Classification (ASJC) codes

  • ???subjectarea.asjc.2700.2730???
  • ???subjectarea.asjc.1300.1306???

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